One workweek of mild sleep restriction adversely impacts sleepiness, performance and pro-inflammatory cytokines. Many individuals try to overcome these adverse effects by extending their sleep on weekends. To assess whether extended recovery sleep reverses the effects of mild sleep restriction on sleepiness/alertness, inflammation and stress hormones, 30 healthy, young men and women (mean age ±SD, 24.7 ± 3.5; mean body mass index ±SD, 23.6 ± 2.4 kg/m2) participated in a sleep laboratory experiment of 13 nights [4 baseline nights (8h/night), followed by 6 sleep restriction nights (6h/night) and 3 recovery nights (10h /night)]. Twenty-four-hour profiles of circulating interleukin-6 (IL-6) and cortisol, objective and subjective daytime sleepiness (Multiple Sleep Latency Test and Stanford Sleepiness Scale), and performance (Psychomotor Vigilance Task) were assessed on days 4 (baseline), 10 (after one week of sleep restriction) and 13 (after 2 nights of recovery sleep). Serial 24-h IL-6 plasma levels increased significantly during sleep restriction and returned to baseline after recovery sleep. Serial 24-h cortisol levels during restriction did not change compared to baseline, but after recovery they were significantly lower. Subjective and objective sleepiness increased significantly after restriction and returned to baseline after recovery. In contrast, performance deteriorated significantly after restriction and did not improve after recovery. Extended recovery sleep over the weekend reverses the impact of one workweek of mild sleep restriction on daytime sleepiness, fatigue and IL-6 levels, reduces cortisol levels, but does not correct performance deficits. The long-term effects of a repeated sleep restriction/sleep recovery weekly cycle in humans remain unknown.